The objective of this study was to determine the effects of replacement doses of testosterone on fat-free mass and muscle size in healthy hypogonadal men, in the setting of controlled nutritional intake and exercise level. Seven hypogonadal men, 19-47 years of age, after at least a 12 week washout from previous androgen therapy, were treated for ten weeks with testosterone enanthate 100 mg/wk by intra-muscular injections. Body weight, fat-free mass measured by underwater weighing and deuterated water dilution, and muscle size measured by magnetic resonance imaging were assessed before and after treatment. Energy and protein intake were standardized at 35 kcal/kg/day and 1.5 g/kg/day, respectively. Body weight increased significantly from 79.2(5 y to 83.7(5.7 kg after 10 weeks of testosterone replacement therapy (weight gain, 4.5(0.6 kg, P=0.00064). Fat-free mass measured by underwater weighing, increased from 56.0(2.5 to 60.9(2.2 kg (change, +5.0(0.7 kg, P=0.0004), but pe rcent fat did not significantly change. Similar increases in fat-free mass were observed with the deuterated water method. Measures of protein dynamics including L (1--13-C)leucine turnover, leucine oxidation, and non-oxidative disappearance of leucine did not significantly change after 10 weeks of treatment.